The present invention relates generally to electroporation in-vivo and specifically to apparatus and method for reducing subcutaneous fat deposits and/or for performing virtual face lifts and/or body sculpturing.
xe2x80x9cCosmetic surgeryxe2x80x9d is a phrase used to describe broadly surgical changes made to a human body with the usual, though not always, justification of enhancing appearance. This area of medical practice constitutes an ever-growing industry around the world. Obviously, where such a procedure fails to deliver an enhanced appearance, the procedure fails to meet the desired goal. One of the reasons that the majority of current procedures fail to deliver upon their promise is that, for the most part, current procedures are invasive, requiring incisions and suturing, and can have serious and unpleasant side effects, including but not limited to scarring, infection, and loss of sensation.
One of the more common forms of cosmetic surgery is the xe2x80x9cface-lift.xe2x80x9d A face-lift is intended to enhance facial appearance by removing excess facial skin and tightening the remaining skin, thus removing wrinkles. A face-lift is traditionally performed by cutting and removing portions of the skin and underlying tissues on the face and neck. Two incisions are made around the ears and the skin on the face and neck is separated from the subcutaneous tissues. The skin is stretched, excess tissue and skin are removed by cutting with a scissors or scalpel, and the skin is pulled back and sutured around the ears. The tissue tightening occurs after healing of the incisions because less skin covers the same area of the face and neck and also because of the scars formed on the injured areas are contracting during the healing process.
Traditional face-lift procedures are not without potential drawbacks and side effects. One drawback of traditional cosmetic surgery is related to the use of scalpel and scissors. The use of these devices sometimes leads to significant bleeding, nerve damage, possible infection and/or lack of blood supply to some areas on the skin after operation. Discoloration of the skin, alopecia (boldness), is another possible side effect of the standard cosmetic surgery. The overall quality of the results of the surgery is also sometimes disappointing to the patients because of possible over-corrections, leading to undesired changes in the facial expression. Additionally, face-lift procedures require a long recovery period before swelling and bruising subside.
The use of lasers to improve the appearance of the skin has been also developed. Traditional laser resurfacing involves application of laser radiation to the external layer of the skinxe2x80x94the epidermis. Destruction of the epidermis leads to rejuvenation of the epidermis layer. The drawback of the laser resurfacing procedure is possible discoloration of the skin (red face) that can be permanent.
Another laser procedure involves using optical fibers for irradiation of the subcutaneous tissues, such as disclosed in U.S. Pat. No. Re36,903. This procedure is invasive and requires multiple surgical incisions for introduction of the optical fibers under the skin. The fibers deliver pulsed optical radiation that destroys the subcutaneous tissues as the tip of the fiber moves along predetermined lines on the face or neck. Debulking the subcutaneous fat and limited injury to the dermis along the multiple lines of the laser treatment results in contraction of the skin during the healing process, ultimately providing the face lift. The drawback of the method is its high price and possibility of infection.
Electrosurgical devices and methods utilizing high frequency electrical energy to treat a patient""s skin, including resurfacing procedures and removal of pigmentation, scars, tattoos and hairs have been developed lately, such as disclosed in U.S. Pat. No. 6,264,652. The principle drawback of this technology is collateral damage to the surrounding and underlying tissues, which can lead to forming scars and skin discoloration.
Other forms of cosmetic surgery are also known. One example is liposuction, which is an invasive procedure that involves inserting a suction device under the skin and removing fat tissues. As with other invasive surgical procedures, there is always a risk of infection. In addition, because of the invasive nature of the procedure, physicians usually try to minimize the number of times the procedure must be performed and thus will remove as much fat tissue as possible during each procedure. Unfortunately, this procedure has resulted in patient deaths when too much tissue was removed. Assuming successful removal of excess fat tissue, further invasive surgery may be required to accomplish desired skin tightening.
The prior art to date, then, does not meet the desired goal of performing cosmetic surgery in a non-invasive manner while causing minimal or no scarring of the exterior surface of the skin and at the same time resulting in the skin tightening.
The term xe2x80x9celectroporationxe2x80x9d (EP) is used herein to refer to the use of a pulsed electric field to induce microscopic pores in the membranes of living cells. Living cells include a biological membrane, also commonly called a cell wall, that separates the inner volume of a cell, or cytosol, from the extracellular space, which is filled with lymph. This membrane performs several important functions, not the least of which is maintaining gradients of concentration of essential metabolic agents across the membrane. This task is performed by active protein transporters, built in the membrane and providing transport of the metabolites via controlled openings in the membrane. Inducing relatively large pores in the cell membrane by electroporation creates the opportunity for a fluid communication through the pores between the cytosol and the extracellular space that may lead to a drastic reduction of these vitally important gradients of concentrations of the metabolic agents. Uncontrolled exchange of metabolic agents, such as ions of sodium, potassium, and calcium between a living cell and the extracellular space imposes on the cell intensive biochemical stress.
When a cell is undergoing biochemical stresses the major biochemical parameters of the cell are out of equilibrium and the cell cannot perform its routine functions. In an attempt to repair itself, the cell starts worling in a damage control mode. The active protein transporters, or pumps, routinely providing transport of various metabolic agents, especially proteins, across membranes, use the energy of hydrogen or sodium positive ions passing from a positive potential of the intracellular space to a negative potential of the cytosol, or for the opposite direction the energy of a negative chlorine ion. This energy supply is provided by maintaining the potential difference across the membrane which, in turn, is linked to the difference in concentrations of sodium and potassium ions across the membrane. When this potential difference is too low, thousands of the active transporters find themselves out of power. Invasion of very high concentration of calcium ions from the interstitial space between cells, where the calcium ion concentration is about 100 times higher than in the cytosol, triggers an emergency production of actin filaments across the large pores in the membrane in an attempt of the cell to bridge the edges of the pores, pull the edges together, and thereby seal the membrane. In muscle cells the calcium ion invasion may cause lethal structural damage by forcing the cell to over-contract and rupture itself. Small pores in the membrane created by a relatively short electric pulse can reseal themselves spontaneously and almost instantaneously after the removal of electric field. No significant damage to the cell is done in this case. Contrary to that, larger pores may become meta-stable with very long life time and cause irreversible damage. It can be said that, depending on the number, effective diameter and life time of pores in the membrane, electroporation of the cell may result in significant metabolic or structural injury of the cell and/or its death. The cause of cell death after electroporation is believed to be an irreversible chemical imbalance and structural damage resulted from the fluid communication of the cytosol and the extracellular environment.
Below a certain limit of the electric field no pores are induced at all. This limit, usually referred to as the xe2x80x9clower EP limitxe2x80x9d of electroporation, is different for different cells, depending, in part, on their sizes in an inverse relationship. That is, pores are induced in larger cells with smaller electric fields while smaller cells require larger electric fields. Above the lower EP limit the number of pores and their effective diameter increase with both the amplitude and duration of the electric field pulses.
Removing the electric field pulses enables the induced pores to reseal. This process of resealing of the pores and the ability of the cell to repair itself, discussed briefly above, currently is not well understood. The current understanding is that there is a significant range of electric field amplitudes and pulse durations in which cells survive electroporation and restore their viability thereafter. An electroporated cell may have open pores for as long as many minutes and still survive. The range of electric field amplitudes and pulse durations in which cells survive is successfully used in current biomedical practice for gene transfer and drug delivery inside living cells.
Nevertheless, the survivability of electroporated cells is limited. As the electric field amplitude and/or duration of pulses, increases, this limit, usually referred to as the xe2x80x9cupper EP limitxe2x80x9d of electroporation, is inevitably achieved. Above the upper EP limit, the number and sizes of pores in the cellular membrane become too large for a cell to survive. Multiple pulses cause approximately the same effect on the cells as one pulse with duration equal to the total duration of all applied pulses. After application of an electrical pulse above the upper electroporation limit the cell cannot repair itself by any spontaneous or biological process and dies. The upper EP limit is defined by the combinations of the amplitudes of electric field and pulse durations that cause cellular death.
The vulnerability of cells to electroporation depends on their size: the larger the cell, the lower the electric field and duration of a pulse capable of killing it. If cells of different sizes are exposed to the same electric field, the largest cells will die first. Thus, this ability of electroporation to discriminate cells by their sizes may be used to selectively kill large cells in the human body.
In the previously referred to application for United States patent application entitled xe2x80x9cApparatus and Method for Reducing Subcutaneous Fat Deposits, Virtual Face Lift and Body Sculpting by Electroporationxe2x80x9d, Ser. No. 09/931,672, filed Aug. 17, 2001, an apparatus and method for performing non-invasive treatment of the human face and body by electroporation in lieu of cosmetic surgery is disclosed. The apparatus comprises a high voltage pulse generator and an applicator having two or more electrodes utilized in close mechanical and electrical proximity with the patient""s skin to apply electrical pulses thereto. The applicator may include at least two electrodes with one electrode having a sharp tip and another having a flat surface. High voltage pulses delivered to the electrodes create at the tip of the sharp electrode an electric field high enough to cause death of relatively large subcutaneous fat cells by electroporation. Moving the electrode tip along the skin creates a line of dead subcutaneous fat cells, which later are metabolized by the body. Multiple applications of the electrode along predetermined lines on the face or neck create shrinkage of the skin and the subcutaneous fat reduction under the treated area.
The electroporation in-vivo, employed in the disclosed method of treatment of subcutaneous fat, involves high voltage pulses applied to the skin of a patient. Delivery of such pulses, however, may result in the patient experiencing an unpleasant sensation of small, but palpable electric jolt or shock during pulsing.
The electric current passing the skin and surrounding tissues between electrodes excites sensory nerves and may cause a discomfort sensation or even pain. This perception is the end result of a process that begins with stimulation of a peripheral sensory nerve and culminating in the conscious awareness of the pain at the cerebral cortex. There are several levels of organization within the central nervous system at which the perception of pain may be interrupted, thereby providing the opportunity to prevent the sensation of pain by a patient.
The perception of pain begins with stimulation of a distal peripheral sensory nerve. The stimulation signal travels to a higher level of sensory collection, which is at the dorsal sensory nerve root ganglion just laterally of the spinal cord. The signal enters the spinal cord and ascends to the brain stem, from which it traverses onto the sensory strip along the cerebral cortex. Each area of the cortex in this strip represents a surface area of the body in a fashion known as the homunculus distribution of the cerebral cortex.
Various procedures and drugs have been employed in the past to interrupt the perception of pain at these various levels. Peripheral nerve blockade is achieved through various methods, the most common of which is a local nerve block with medications such as lidocaine injected at the procedure site.
A variety of medications can be used in local, regional and general anesthesia. Drugs are available for local tissue injection providing a direct anesthetic block at the sensory nerve ends. Other drugs are used for intravenous delivery and disseminate throughout the entire body and produce a general anesthesia effect. Intermediate to this, medications have been developed for direct injection into nerve bundles to provide a regional type of anesthetic block. Such examples of regional anesthesia are axillary nerve blocks putting the arm to sleep, sacral nerve blocks putting the back of the leg to sleep, and saddle blocks or epidural blocks that render the entire lower half of the body anesthetized.
Anesthetic drugs are efficient in reducing or blocking the sensation of pain, but they have their own drawbacks. They can have toxic side effects or cause allergic reactions in certain patients. Also, they can significantly increase the cost of surgical or other procedures. Whenever it is possible, it is desirable to avoid usage of the pharmacological drugs for pain control.
The Gate Control Theory of pain was initially proposed in 1965 by Melzack and Wall and now is widely accepted by the scientific community. The Gate Control Theory provides that large and small diameter nerve fibers, both of which carry pain signals, travel through the same xe2x80x9cgate mechanism.xe2x80x9d The theory further provides that activated large nerve fibers can inhibit the transmission of a pain signal by the smaller nerves fibers.
Chemicals released as a response to the pain stimuli also influence whether the gate is open or closed for the brain to receive the pain signal. This lead to the theory that the pain signals can be interfered with by stimulating the periphery of the pain site, the appropriate signal-carrying nerves at the spinal cod, or particular corresponding areas in the brain stem or cerebral cortex. It is generally recognized that the xe2x80x9cPain Gatexe2x80x9d can be shut by stimulating nerves responsible for carrying the touch signal (mechanoreceptors). This finding enables the relief of pain through massage techniques, rubbing, and also the application of hot wheat bags or cold ice packs. The Gate can also be shut by stimulating the release of endogenous opioid-type chemicals that are released by the body in response to the pain stimuli.
One of non-drug mediated pain control techniques is called Transcutaneous Electrical Nerve Stimulation (TENS). It is based on a discovery that application of electrical current to the body can also interfere with transmission of pain signals along the nerve pathways and give patients a significant analgesic (pain relieving) effect. The Gate Control Theory of pain suggests that this effect is mediated by endogenous pain relieving chemicals, released by the body in response to the electric transcutaneous stimulation, consequently blocking the ability of the nerve to transmit pain signals. If a large nerve, responsible for transmission of perception of heat or touch, is carrying periodic signals from the endings on the skins, the Gate for the pain signals transmitted to the spinal cord via small nerves are closed and the pain is reduced.
Currently TENS is used primarily for symptomatic relief and management of chronic intractable pain or as an adjunctive treatment in the management of post-surgical or post-traumatic acute pain. TENS usually involves the application of a sequence of short electrical pulses with relatively low repetition rate intended to affect the nervous system in such a way as to suppress the sensation of pain from acute or chronic injury. Typically, two electrodes are secured to the skin at appropriately selected locations. Mild electrical impulses are then passed into the skin through the electrodes to interact with the underlying nerves over the treatment site. As a symptomatic treatment, TENS has proven effective in the reduction of both chronic and acute pain of patients.
It would be desirable to have a method and apparatus that could mitigate the discomfort created by the electroporation in-vivo without resorting to anesthetic drugs using non-pharmocological aids.
The present invention provides an apparatus and method for creation of a controlled injury or alteration to the subcutaneous tissue and/or underside of the dermis, with the following healing process leading to the contraction of the skin; and/or to the controlled destruction of fat cells, leading to their permanent loss, all with increased comfort for the patient. In the present invention the damage to the subcutaneous tissue, underside of the dermis, and/or fat cells is caused by electroporation. Patient discomfort associated with using electroporation in-vivo for cosmetic purposes is attacked by an apparatus and a method according to the present invention. To do so, apparatus and method relating to TENS is incorporated into the electroporation apparatus used for reducing subcutaneous fat deposits, virtual face lift and body sculpturing to relieve a discomfort that may arise from electroporation treatment. The new apparatus is provided with an additional low voltage pulse generator connected to electrodes placed on a treatment site of the patient""s body. Improved comfort for the patients is achieved by delivering a sequence of low voltage pulses that provide transcutaneous electrical nerve stimulation, thereby substantially blocking the neural messages of discomfort or pain that may arise from the high voltage pulsing. To create some initial analgesic effect, a sequence of TENS pulses may be applied before delivery begins of an electroporation pulse, with the TENS pulses continuing for some time after. The analgesic effect is mediated by a release of natural body analgesics triggered by TENS.
Another feature of the current invention is that the electroporation pulses delivered to the treatment site are synchronized with the TENS pulses. Thus, each electroporation pulse may be applied with a delay after a TENS pulse, namely during a refractory period for the surrounding nerves caused by the TENS pulse. The refractory period is a state of a nerve cell that exists for a short period of time after the onset of an excitation, approximately 0.5 milliseconds, and is characterized by an absolute inability of the nerve to be excited by a stimulus, no matter how intense this stimulus is. This is so called xe2x80x9cabsolute refractory periodxe2x80x9d. In the next 1.0 ms the ability of the nerve to be excited gradually returns to a normal level, but the threshold of excitation during this period is significantly higher than its normal level. This is the so-called xe2x80x9crelative refractory periodxe2x80x9d. Thus, according to the current invention, the high voltage pulses are applied to the patient""s skin only when all or substantially all of the nerves surrounding the treatment site are in the refractory state created by a previous application of a TENS pulse. Application of EP pulses during the refractory period will provide significant improvement of the patient""s comfort during an electroporation procedure.
The present invention, as well as its various features and advantages, will become evident to those skilled in the art when the following description of the invention is read in conjunction with the accompanying drawings and claims. Throughout the drawings, like numerals refer to similar or identical parts.